tbuckley/cabot-search huggingface dataset:
European Association of Urology (EAU) Testicular Cancer Guidelines Panel: A new prognostic factor risk group classification for patients with clinical stage 1 seminoma in active surveillance.
Authors: Joost Boormans, Richard J Sylvester, Lynn Anson-Cartwright, Rachel Glicksman, Robert James Hamilton, Gedske Daugaard, Jakob Lauritsen, Thomas Wagner, Barbara Avuzzi, Nicola Nicolai, Jorge Aparicio, Xavier Garcia del Muro, Pilar Laguna
Journal: Journal of Clinical Oncology (2023)

410 Background: Between 4%- 30% of patients with clinical stage 1 (CS I) seminoma testis (ST) in active surveillance (AS) relapse depending on pathological risk factors tumor size (TS) and rete testis invasion (RTI). The level of evidence supporting these pathological risk factors in clinical decision-making is low due to heterogeneous study design and reporting and the difficulty to analyze patient subgroups according to combination of these factors. The objectives of the present study were to identify the most important pathological prognostic factors predicting relapse in CS I seminoma patients with normal post-orchidectomy serum tumor marker (STM) levels in AS and to construct risk-groups for guiding treatment decision-making and follow-up. Methods: Individual patient data from 1016 CS I-ST patients diagnosed between February 1994 and January 2019 in AS were collected from 9 institutions. Central pathology review was not routinely performed in all institutions; therefore, pagetoid and stromal RTI were not differentiated explicitly in most cases. Assessing patient age, pre-orchidectomy STM b-human chorionic gonadotropin and lactate dehydrogenase, pathological TS, RTI, lympho-vascular invasion (LVI), multi-focality, and GCNIS, multivariable Cox proportional hazards regression models were fit to identify the most important prognostic factors for the time to first relapse by imaging and/or markers (primary endpoint). Probabilities of relapse were estimated using Kaplan-Meier curves. Results: After median follow-up of 7.7 years, 149 (14.7%) patients relapsed, 104 identified by imaging alone, 44 by imaging with elevated STMs and 1 by elevated STMs alone. Excluding 18 patients with unknown LVI from the multivariable analyses, TS (≤ 2 cm, between 2 and 5 cm, &gt; 5 cm), presence of RTI and presence of LVI were used to form three risk groups: very low, low and high-risk (Table). Five-years probability of relapse varied from 8% in the very low risk-group to 44% in the high risk-group. The new model outperformed the current model with TS &lt; 4cm vs ≥ 4 and RTI (Harrell's C index 0.65 vs 0.61) and identifies a subgroup of patients with a higher risk of relapse. Conclusions: The new risk-group stratification for CS I -ST patients in AS outperforms the histopathological model based on TS and RTI. It will serve to better inform patients on the risk of relapse during follow-up after orchidectomy but requires an independent validation. [Table: see text]
Phase 3 KEYNOTE-905/EV-303: Perioperative pembrolizumab (pembro) or pembro + enfortumab vedotin (EV) for muscle-invasive bladder cancer (MIBC).
Authors: Andrea Necchi, Jens Bedke, Matt D. Galsky, Neal D. Shore, Elizabeth R. Plimack, Evanguelos Xylinas, Calvin Jia, Tammy Hennika, Blanca Homet Moreno, Alfred Alfred Witjes
Journal: Journal of Clinical Oncology (2023)

TPS585 Background: Standard of care for MIBC is neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy + pelvic lymph node dissection (RC + PLND). However, a substantial proportion of patients (pts) with MIBC are ineligible to receive cisplatin-based chemotherapy. In the phase 1b/2 KEYNOTE-869/EV-103 study, promising antitumor activity was shown in cisplatin-ineligible pts with metastatic urothelial carcinoma treated with the PD-1 inhibitor pembro combined with the nectin-4–directed antibody-drug conjugate EV. This multicenter, open-label, randomized, phase 3 KEYNOTE-905/EV-303 study (NCT03924895) is designed to evaluate the efficacy and safety of perioperative pembro alone or in combination with EV compared with RC + PLND alone in pts with MIBC who are ineligible for or decline cisplatin-based treatment. Methods: Approximately 857 adults who are cisplatin ineligible or decline cisplatin-based treatment with treatment-naive MIBC (T2-T4aN0M0 or T1-T4aN1M0), have an Eastern Cooperative Oncology Group performance status score of 0-2, and have a predominant (≥50%) urothelial histology will be randomly assigned to arm A (neoadjuvant pembro 200 mg intravenously [IV] every 3 weeks [Q3W] up to 3 cycles followed by RC + PLND and adjuvant pembro 200 mg IV Q3W up to 14 cycles), arm B (RC + PLND followed by observation), or arm C (neoadjuvant EV 1.25 mg/kg + pembro 200 mg IV Q3W up to 3 cycles followed by RC + PLND and adjuvant EV + pembro up to 6 cycles and adjuvant pembro 200 mg IV Q3W up to 8 cycles). In both the neoadjuvant and adjuvant phases of arm C, pembro will be administered on day 1 and EV will be administered on days 1 and 8 of each cycle. Dual primary end points are pathologic complete response as assessed by central pathologic review and event-free survival. Secondary end points include overall survival, disease-free survival, pathologic downstaging rates, and safety and tolerability. Enrollment is ongoing in Africa, Asia, Europe, and North America. Clinical trial information: NCT03924895 .
Comparison of transperineal and transrectal biopsy approaches to detect clinically significant prostate cancer in patients undergoing MRI fusion prostate biopsy: A lesion level analysis.
Authors: Andrew Wood, Prajit Khooblall, Tarik Benidir, Jennifer Bullen, Ryan Ward, Andrei Purysko, Christopher J. Weight
Journal: Journal of Clinical Oncology (2023)

320 Background: The use of transperineal (TP) prostate biopsy has gained in popularity due to reduced risk of infectious events, however evidence regarding cancer detection rates versus transrectal (TR) prostate biopsy is lacking. Our objective was to examine whether transperineal (TP) MRI-fusion targeted prostate biopsy (MRI-TBx) resulted in improved detection of clinically significant prostate cancer (csPCa), defined as International Society of Urological Pathology (ISUP) grade group ≥2, as compared to TR MRI-TBx. Methods: Retrospective review of all patients who underwent MRI-TBx at a tertiary care academic center. A cohort of patients who underwent TP MRI-TBx was compared to a second cohort of patients who underwent TR MRI-TBx. The primary outcome of interest was detection of csPCa, however detection of ISUP grade group 1 prostate cancer (GG1 PCa) was also examined. Analyses were performed on a lesion level basis. Multivariable logistic regression analyses were performed to assess for predictors of csPCa detection. Results: A total of 389 and 1144 lesions from 303 and 836 patients who underwent TP MRI-TBx vs TR MRI-TBx respectively were included in the analysis. The detection of both csPCa (39.6% vs 29.6%, p &lt;0.001) and GG1 PCa (34.4% vs 21.1%, p &lt;0.001) was higher for TP MRI-TBx vs. TR MRI-TBx. On multivariable analysis adjusted for age, prior biopsy status, Prostate Imaging–Reporting and Data System (PIRADS) score, prostate volume, PSA, size of PIRADS lesion, and zone of PIRADS lesion, TP MRI-TBx remained an independent predictor of csPCa (odds ratio [OR] 1.49, 95% CI 1.13-1.98). Surprisingly, transperineal biopsy was not a significant predictor of csPCa for Transition zone lesions (OR 1.24, p = 0.35), but was for Peripheral zone lesions (OR = 1.84, p &lt; 0.001). Conclusions: Performance of TP MRI-TBx demonstrates improved detection of both csPCa and GG1 PCa. This difference is not dependent on anterior/transition zone location. This has important implications in risk assessment for localized prostate cancer, including counseling for active surveillance and definitive management strategies. [Table: see text]
Length and Gleason pattern at positive surgical margin after radical prostatectomy to assess risk of postoperative recurrence in localized prostate cancer.
Authors: Masashi Kato, Toyonori Tsuzuki
Journal: Journal of Clinical Oncology (2023)

359 Background: The prostatic apex is most popular location of positive surgical margin (PSM) at radical prostatectomy (RP) and the frequency of apex is reported to be about 20-40% of all positive cases. Prostatic apex is also reported to lack a well-defined capsule. Some recommendation suggest that reporting require location of a PSM, as well as length of PSM, though there are also reports that these classifications is inadequate in some patients. In addition, there is a lack of tumor grade at PSM in these recommendations. This study aims to investigate the impact of location, number, length, and tumor grade at PSM on biochemical recurrence (BCR) after RP. Methods: We retrospectively evaluated 1013 patients with prostate cancer who underwent radical prostatectomy without neoadjuvant or adjuvant therapy at the hospitals that the authors were affiliated with between 2005 and 2013. All prostatectomy specimen slides were reviewed by a single genitourinary pathologist according to ISUP 2019 criteria. PSM were subcategorized according to the length of PSM (≤ 5mm or &gt; 5mm), Gleason pattern (GP3 vs. GP4 or 5) at PSM, the number (single or multiple), and the location (apex-only or others). Results: The median patient age was 67 (range, 45–80) years. The median initial PSA was 6.8 ng/ml (0.4–82 ng/ml). The median follow-up period was 69 (0.7–135) months. Pathological T stage was in 73% of pT2 (n=733), 22% of pT3a (n=229), and 4% of pT3b (n=41). PSM was found in 377 cases. Length of margin is total and 5mm in median. PSM was found at apex-only in 187 cases (50%), and others showed other single location or multiple PSM. Single PSM is found in 293 cases (78%). GP3 at PSM was found in 130 cases, GP4 in 214, and GP5 in 33. GP3 at PSM tended to be more common in apex-only PSM. GP5, extra prostatic extension (EPE), seminal vesicle invasion, IDC-P, and PSM were significant in all the patients to predict BCR. Among the patients with PSM, multivariate analysis showed that length and GP at PSM were significantly strong factors and were stronger than location and number of PSM. The prognosis in pT2 patients with PSM were significantly subcategorized into 3 groups according to the length and GP at PSM (P&lt;0.001). Conclusions: We proposed the recurrence risk classification based on the length and the GP at PSM to predict BCR after radical prostatectomy. It is useful for prognosis prediction and high-risk group should be considered for adjuvant radiation and/or hormonal therapy in postoperative care.
Partial gland ablation outcomes for localized prostate cancer in patients with MRI-visible and MRI-invisible lesions.
Authors: Alec Zhu, Sofia Gereta, Judith Stangl-Kremser, Daniel Margolis, Leonardo Daniel Borregales, Spyridon P. Basourakos, Timothy D McClure, Jim C. Hu
Journal: Journal of Clinical Oncology (2023)

368 Background: Partial gland ablation (PGA) for MRI-invisible prostate cancer (PCa) remains controversial, and we compared treatment failure rates, adverse events, and health-related quality-of-life outcomes (HRQoL) following PGA in subjects with MRI-visible vs. MRI-invisible lesions. Methods: Retrospective review was done of primary PGA therapy (cryoablation, irreversible electroporation, and high-intensity focused ultrasound) performed between January 2017 and 2022 at Weill Cornell Medical Center. Analysis was restricted to men with at least one post-PGA prostate biopsy. Men with PCa on systematic biopsy outside of the MRI-targeted zone were categorized as having MRI-invisible lesions. Failure of PGA was defined as persistence or recurrence of Gleason grade group (GGG) ≥2 on surveillance biopsy for subjects diagnosed with GGG ≥2 PCa. For patients treated for GGG 1 PCa, failure was defined by the detection of GGG ≥1 PCa. Adverse events were captured by the Clavien-Dindo classification and HRQoL outcomes were captured by the Expanded Prostate Cancer Index-Clinical Practice (EPIC-CP). Groups were compared using Pearson’s chi-squared test and the 2-sided Wilcoxon-Mann-Whitney test. Results: Out of 115 men were treated for primary prostate cancer, 89 men had at least one surveillance biopsy performed, and 87 men had available pre-treatment MRI data. Out 79 subjects treated with MRI-visible lesions and 34 subjects treated with MRI-invisible lesions, 59 and 28 subjects, respectively, had surveillance biopsy data. Median (IQR) follow-up was 15.5 months (7.7-25.5) in the overall cohort; median follow-up was not significantly different between the MRI-visible and MRI-invisible groups (15 vs. 15 months, p-value=0.766). Failure of PGA occurred in 43 (48.3%) of total subjects. Failure of PGA was not significantly different between the MRI-visible and MRI-invisible groups (50.9% vs. 42.9%, p-value=0.502). Mean total EPIC-CP scores were not significantly different between both groups at baseline, 3, 6, and 12 months after PGA. Additionally, rates of 30-day complications were not significantly different between both groups. Conclusions: Failure is evident in almost half of patients treated with PGA therapy. Oncologic and functional treatment outcomes after focal therapy are similar between patients with MRI-visible and MRI-invisible lesions. [Table: see text]
Differential expression of PDL-1 and tumour-associated macrophages in N0 and N+ penile cancer.
Authors: Fowz Azhar, Ashwin Sachdeva, Claire Alexandre Hart, Mick D. Brown, Vijay Sangar, Arie Parnham, Maurice Lau, Pedro Oliveria, Noel W Clarke
Journal: Journal of Clinical Oncology (2023)

12 Background: Penile squamous cell carcinoma (PSCC) is rare, representing 0.4-0.6% of all male malignancies in the global-north, as compared with 2-10% in the global-south. Overall survival (OS) dramatically decreases with increased lymph node metastases (LNM). Increased prevalence of pro-tumorigenic M2 CD163+ tumour associated macrophages (TAM) is associated with poor PSCC OS, whereas increased prevalence of the generic M1/2 CD68+ TAMs is associated with better PSCC OS. PDL-1 expression has been noted in 40-60% of PSCC primary lesions. However, there is a paucity of evidence on the overall tumour immune microenvironment (TME) within penile LNM disease. This study describes the relationship between PDL-1 expression and TAMs within the TME of the primary tumour and paired LNMs, with the goal of predicting the utility of PD-1 inhibitors in clinical trials in PSCC. Methods: The Ventana Discovery ULTRA platform was used to optimise a 7-marker multiplex immunofluorescence panel on whole FFPE sections of primary and LNM lesions. Multispectral images were captured using a Vectra 3 microscope. Single cell spatial analysis was performed using HALO software, with statistical analysis of data using R 4.2.1. Results: 52 cases with differing LN stages were identified: N0 (N=20); N1/N2 (N=21); N3 (N=11). Increased expression of PDL-1 was noted at the primary lesion invasive margin (IM) of N+, compared with N0 patients. High expression in inguinal LNMs (iLN+) and pelvic LNMs (pLN+) was also observed, with no expression detected in microscopically normal, tumour free LNs (LN-) in the N0 cohort. More CD163+ M2 TAMs were observed at the IM of N+ compared with N0. However, no significant difference was observed between the three LN groups. M1/2 CD68+ TAMs were more prevalent within pLN+ vs iLN+ or LN-. There was no significant difference in M1/2 CD68+ TAMs number at the IM. Conclusions: Our data highlights increased prevalence of M2 CD163+ TAMs within the IM is associated with LNM. Increased presence of CD68+ M1/2 TAMs in pLN+ may represent active inflammation at the leading microscopic edge of metastatic deposits. A significant difference in the expression of PDL-1 between localised and metastatic disease at both primary and LN location is noted. High PDL-1 expression at the IM of the primary lesion is associated with increased LNMs, where PDL-1 expression is significantly higher as compared to LN-. This study supports the rationale for the use of anti-PD-1/PDL-1 therapies in patients with LNM disease.
DNA alterations in papillary renal cancer.
Authors: Francesca Jackson-Spence, Charlotte Ackerman, Bernadett Szabados, Charlotte Toms, Agne Jovaisaite, Rachel Gunnell, Cristina Suárez, James Larkin, Poulam Patel, Begoña Pérez Valderrama, Alejo Rodriguez-Vida, Hilary Glen, Fiona C. Thistlethwaite, Christy Ralph, Gopalakrishnan Srinivasan, Maria Jose Mendez-Vidal, Aleksandra Markovets, Ryan James Hartmaier, Thomas Powles
Journal: Journal of Clinical Oncology (2023)

725 Background: The characterisation of DNA alternations in papillary renal cancer (PRC) is unclear. The CALYPSO trial (NCT02819596) prospectively evaluated combination therapy of savolitinib (MET inhibitor) and durvalumab (PD-L1 inhibitor) in PRC. The trial showed high response rates (RR) in the MET-driven population. Here we explore the relationship between MET, PD-L1 and TMB in these tumours and the relevance of other biomarkers including PIK3CA, PTEN and KRAS. Methods: FoundationOne analysis from 41 samples of PRC patients enrolled on the CALYPSO trial was performed. The relevance of co-positivity between MET/PD-L1 and MET/TMB as well as analysis of other DNA alterations such as PIK3CA, PTEN and KRAS was explored. Outcome parameters were correlated with RR, PFS and OS. Results: 41% of patients were MET-driven, 66% were PD-L1+ (vCPS≥1) and 3% were TMB &gt;10mut/Mb. Further testing used TMB ≥ median (2.52mut/Mb) 32% of patients were both MET-driven and PD-L1+. 17% of patients were both MET-driven and TMB ≥ median. RR and survival outcomes for combinations are shown in the table. The overall RR in MET driven and non-MET-driven patients was 52.9% and 13%, respectively. The median PFS and OS in the MET-driven group was 12.0 months (95% CI: 2.9-19.4) and 27.4 months (95% CI: 9.3-not reached [NR]), respectively, compared to a median PFS and OS in the non-MET-driven group of 2.7 months (95% CI: 0.5-5.0) and 7.5 months (95% CI: 0.0-16.0), respectively. PIK3CA, PTEN and KRAS mutations occurred in 1, 4 and 2 patients, with RR of 0% (0/1), 25% (1/4) and 50% (1/2), in the PIK3CA, PTEN and KRAS groups, respectively. Conclusions: MET-driven papillary cancers have low mutational burden, but high PD-L1 expression. Small patient numbers limit definitive conclusions, but responses occur irrespective of the immune biomarkers investigated. Other DNA alterations are rare and did not appear to influence outcomes in this cohort. These data support the design of the SAMETA trial (NCT05043090), further investigating the savolitinib and durvalumab combination. [Table: see text]
Preliminary findings of G8 and G8-modified as screening tools associated with quality of life in elderly patients with prostate, renal or bladder neoplasms in a Brazilian cancer center.
Authors: Ingrid Felix Felix Modesto, Aldo A. Dettino
Journal: Journal of Clinical Oncology (2023)

122 Background: Population aging and cancer increased incidence are a public health challenge, as the elderly vary widely in terms of health status and aging process. Aiming at therapeutic efficacy and minimization of toxicities, treatment should be individualized. To aid in clinical decision and patient (pt) management, screening tools use is recommended, such as the G8 and the G8-modified (G8m), which identify geriatric problems: scored as abnormal when ≤ 14 and ≥6, respectively. These scales include health status self-assessment, which can be investigated by specific tools as EQ-5D-5L. The objective is to compare the G8 and G8m scales as screening tools in Brazilians ≥ 60 years old with urological tumors and describe Quality of Life using the Visual Analogue Scale of EQ-5D-5L (EQ VAS), which scores from 0-100 (higher better). Methods: Sociodemographic data were collected, and scales G8, G8m and EQ-5D-5L were applied to elderly people ≥ 60 years old with urologic cancer diagnosed within 6 months or prior to a change in therapeutic strategy, from Feb to Sep 2022. Statistical analyzes were performed, such as means, median, standard deviation and proportions, as well as comparisons of G8 total score versus G8m, using Kappa Coefficient. Fisher's Exact Test was used to analyze these scores related to sociodemographic data and the Pearson Correlation test to verify the relationship of the scores with the EQ VAS. Results: 43 pt aged ≥ 60 completed G8 with a mean score of 13,7(±2,2), G8m with 7,7 (±6,6) and EQ VAS 81,5 (±14,9). The mean age was 72,7 (±8,7) and 100% were men and 27 (62,8%) were white; furthermore, 9 (20,9%) lived alone. The most frequent cancer type was prostate 34(79,1%), followed by renal 5 (11,6%). 36 (83.7%) pt were changing treatment strategy and 7 (16.3%) had a diagnosis within 6 months. A weak agreement of 72.2% between normal G8 and G8m scores was identified (Kappa = 0.435 and p 0.006). A statistically significant association between normal G8m score and married marital status (p=0.039) was found, however there was no statistically significant association between G8 and G8m scores and comorbidities, smoking or polypharmacy. As well as no statistically significant correlation was found between the G8 and G8m scores with the Quality of Life measured by the EQ VAS. Conclusions: G8 and G8m demonstrated similar results in elderly pt with urologic tumors, identifying pt with frailties that are warranting a complete geriatric evaluation. In addition, this study indicates that it is better to assess quality of life using specific instruments, since the G8 and G8m scores were not correlated with the EQ VAS, although the screening scales included self-rated health. We intend to prospectively evaluate the prognostic power in the short term - 6 months, relating it to the quality of life, by the EQ-5D-5L.